The Y-Box Binding Protein 1 Suppresses Alzheimer’s Disease Progression in Two Animal Models

Бобкова, Н. В.; Lyabin, Dmitry N.; Medvinskaya, N. I.; Samokhin, A. N.; Nekrasov, Pavel V.; Нестерова, И. В.; Aleksandrova, I. Yu.; Tatarnikova, Olga; Bobylev, A. G.; Vikhlyantsev, I. M.; Kukharsky, Michail S.; Ustyugov, A. A.; Polyakov, Dmitry; Eliseeva, Irina A.; Kretov, Dmitry A.; Guryanov, Sergey; Ovchinnikov, Lev P.

doi:10.1371/journal.pone.0138867

Cited by 26 publications

(16 citation statements)

References 38 publications

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“…Existing drugs may have certain toxic side effects on cells, and thus, their biocompatibility, biosafety and biodegradability are poor. Moreover, neural stem cells are characterized by low survival rate, slow proliferation, and slow differentiation and maturity . Promoting nerve regeneration through small molecule compounds may be a new therapeutic strategy.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Alzheimer's disease with framework nucleic acids

et al. 2020

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Objectives To provide a new research direction for nerve regeneration and strategy for Alzheimer's disease treatment, tetrahedral DNA nanostructures (TDNs)—novel tetrahedral framework nucleic acid molecule nanoparticles (tFNA) that can inhibit the apoptosis of nerve cells are employed in the experiment. Materials and methods To verify the successful preparation of TDNs, the morphology of TDNs was observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM). The expression of apoptosis‐related genes and proteins was investigated by confocal microscope, flow cytometry, PCR and Western blot to detect the impact of TDNs on the Alzheimer's model. And finally, Morris water maze experiment was used to test behavioural changes and Nissl stain was detected to observe the morphology and quantity of neurons in the hippocampus. Immunofluorescence stain was used to observe the Aβ stain, and TUNEL dyeing was utilized to observe neuronal apoptosis. Results In vitro and in vivo experiments confirm that TDNs, in a specific concentration range, have no toxic or side effects on nerve cells, can effectively inhibit apoptosis in an Alzheimer's disease cell model and effectively improve memory and learning ability in a rat model of Alzheimer's disease. Conclusions These findings suggest that TDNs may be a promising drug for the treatment of Alzheimer's disease.

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Section: Discussionmentioning

confidence: 99%

Treatment of Alzheimer's disease with framework nucleic acids

et al. 2020

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“…First, Y-box-binding protein 1 (YB-1), a highly conserved cold shock domain family protein, regulates G3BP1 via binding to its 5'UTR to activate its translation (Somasekharan et al, 2015). YB-1 has also been linked to neurodegeneration such that YB-1 expression is neuroprotective in a mouse model of sporadic AD (Bobkova et al, 2015). Specifically, intranasal administration of YB-1 into mice induced the formation of YB-1 granules and positively correlated with a reduction in β-amyloid plaques and showed an improvement in short-term working memory (Bobkova et al, 2015).…”

Section: Regulation Of G3b P1 Mrnamentioning

confidence: 99%

“…The authors noted that intact exogenous YB-1 was detectable within cells for at least 2 hours, suggesting that it may be involved in other mechanisms regulating cell survival in conditions of AD-type neurodegeneration (Bobkova et al, 2015).…”

Section: Regulation Of G3b P1 Mrnamentioning

confidence: 99%

“…YB‐1 has also been linked to neurodegeneration such that YB‐1 expression is neuroprotective in a mouse model of sporadic AD (Bobkova et al, 2015). Specifically, intranasal administration of YB‐1 into mice induced the formation of YB‐1 granules and positively correlated with a reduction in β‐amyloid plaques and showed an improvement in short‐term working memory (Bobkova et al, 2015). The authors noted that intact exogenous YB‐1 was detectable within cells for at least 2 hours, suggesting that it may be involved in other mechanisms regulating cell survival in conditions of AD‐type neurodegeneration (Bobkova et al, 2015).…”

Section: Regulation Of G3bp1 Mrnamentioning

confidence: 99%

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The multi‐functional RNA‐binding protein G3BP1 and its potential implication in neurodegenerative disease

Sidibé

Dubinski

Velde

2021

Journal of Neurochemistry

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Since its discovery in 1996 as a RAS-binding partner, Ras-GTPaseactivating protein (GAP)-binding protein 1 (G3BP1) has been linked to a variety of biological processes, molecular functions and cellular compartments (Parker et al., 1996). Initially suggested to play a key role in the Ras signaling pathway via direct binding to Ras, more recent evidence contradicts this potential function (Annibaldi et al., 2011;Xu et al., 2013). Even if this initial function is debated, based on its role in development, RNA metabolism, degradation and stress response, G3BP1 seems to be a jack-of-all-trades protein that is fundamental to cellular homeostasis.

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“…CK1ε also functions as a major regulator of circadian rhythms 60 , leading speculation that these disturbances to CK1ε expression in AD could be related to the sleep disturbances experienced by patients. Previous in vivo experiments have shown that treatment of 5xFAD mice with recombinant nuclease-sensitive element-binding protein 1 (YBOX 1) results in decreased levels of Aβ in the brain, but also inhibits the fibrillization of Aβ 1-42 in vitro 61 . We show that oAβ exposure caused a decrease in phosphorylated YBOX 1 in the exposed neurons (fold change 0.3, p = 0.054).…”

Section: Identified Proteinsmentioning

confidence: 99%

Oligomeric amyloid-β induces early and widespread changes to the proteome in human iPSC-derived neurons

Sackmann

Hallbeck

2020

Sci Rep

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Alzheimer's disease (AD) is the most common form of dementia globally and is characterized by aberrant accumulations of amyloid-beta (Aβ) and tau proteins. oligomeric forms of these proteins are believed to be most relevant to disease progression, with oligomeric amyloid-β (oAβ) particularly implicated in AD. oAβ pathology spreads among interconnected brain regions, but how oAβ induces pathology in these previously unaffected neurons requires further study. Here, we use well characterized ipSc-derived human neurons to study the early changes to the proteome and phosphoproteome after 24 h exposure to oAβ 1-42. Using nLC-MS/MS and label-free quantification, we identified several proteins that are differentially regulated in response to acute oAβ challenge. At this early timepoint, oAβ induced the decrease of TDP-43, heterogeneous nuclear ribonucleoproteins (hnRNPs), and coatomer complex I (COPI) proteins. Conversely, increases were observed in 20 S proteasome subunits and vesicle associated proteins VAMP1/2, as well as the differential phosphorylation of tau at serine 208. These changes show that there are widespread alterations to the neuronal proteome within 24 h of oAβ uptake, including proteins previously not shown to be related to neurodegeneration. this study provides new targets for the further study of early mediators of AD pathogenesis.Alzheimer's disease (AD) is the most prevalent form of dementia globally and is expected to grow substantially along with the aging global population. Much of the research in this field has focused on the pathological hallmarks of AD, amyloid-β (Aβ) and tau, but the way in which these mediators initiate neuronal pathogenesis at the molecular level requires further understanding. An important consideration in the study of AD is the different properties of Aβ assemblies: monomers, oligomers and fibrils. In particular, there is growing evidence to suggest that low molecular weight Aβ oligomers (oAβ) and protofibrils seed the aggregation of naïve Aβ, confer neurotoxicity, and also correlate to cognitive decline, as reviewed in 1-4 . Much of our current understanding of AD comes from the study of long-term exposure to Aβ in animal models, which has provided valuable insight into the effects of chronic exposure to Aβ, but often overlook the initial steps involved in pathogenesis. In order to further our understanding of the acute effects of exposure to oAβ, we challenged human iPSC-derived neurons with oAβ for 24 h and examined the changes to the proteome and phosphoproteome elicited by this acute oAβ treatment. In this way, we aim to elucidate some of the early effects elicited by oAβ upon neurons.During AD, widespread changes occur in the proteome, including the up-and downregulation of disease-related proteins as well as the post-translational modification (PTM) of proteins. PTMs such as phosphorylation greatly affect the function of proteins and are well known to be important for the pathogenesis of neurodegenerative disorders, where detection of phosphorylated proteins are us...

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The Y-Box Binding Protein 1 Suppresses Alzheimer’s Disease Progression in Two Animal Models

Cited by 26 publications

References 38 publications

Treatment of Alzheimer's disease with framework nucleic acids

Treatment of Alzheimer's disease with framework nucleic acids

The multi‐functional RNA‐binding protein G3BP1 and its potential implication in neurodegenerative disease

Oligomeric amyloid-β induces early and widespread changes to the proteome in human iPSC-derived neurons

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